Palliative and Supportive care

EGFRI-Related Skin Toxicity

Information, treatment algorithms and educational materials for healthcare professionals and patients about skin problems that may occur when being treated with anti-EGFR drugs

Multikinase Inhibitor Related Skin Toxicity

Information, treatment algorithms and educational materials for healthcare professionals and patients relating to the management of dermatological toxicities in patients treated with multikinase inhibitors.

Drug-Drug Interactions with Kinase Inhibitors

Information and education online resource for healthcare professionals on drug-drug interactions which can arise from the use of kinase inhibitors

Abstract

Background

Altough anti-angiogenic drugs are widely used in mRCC, the predictive markers for these agents cannot be well defined yet. MGMT is recently shown to be anti-angiogenic and responsible for the anti-proliferative effect of sunitinib in glioblastome cell lines. In preclinical studies, MGMT positive cells demonstrate high sVEGFR-1/VEGFA ratio, increased VEGFR-1 and decreased VEGFR-2.

TGase-2 is known to be responsible for drug resistance, cell proliferation, migration and angiogenesis. In vitro studies showed that TGase-2 inhibits VHL and this leads to increase of HIF-1α and IGF-1R.

Objective

To investigate the predictive and prognostic role of MGMT and TGase-2 in mRCC patients who were treated with sunitinib.

Methods

We analyzed 82 RCC patients retrospectively. 43 of 82 survive without recurrence (non-metastatic group), 39 of 82 were already metastatic at the diagnosis or had metastasis during follow up (metastatic group). Expression of MGMT and TGase-2 proteins were assessed by immunohistochemical (IHC) staining in tissue samples.

In the metastatic group, all patients received sunitinib as anti-angiogenic therapy and the overall survival (OS) analysis of these patients were performed according to time of sunitinib initiation. OS analysis of the entire group (metastatic and non-metastatic) were performed according to the time of diagnosis.

Results

In the metastatic group (n = 39), the ones with low MGMT had median OS of 30 months while ones with high MGMT had median OS of 47 months (p = 0.498). The ones with low TGase-2 had mean OS of 35.2 months while ones with high TGase-2 had mean OS of 27.9 months (p = 0.366).

In the entire group, the ones with low MGMT had mean OS of 115 months while ones with high MGMT had median OS of 189 months (p = 0.498). The ones with low TGase-2 had mean OS of 212 months while ones with high TGase-2 had mean OS of 133 months (p = 0.281).

Conclusions

Higher MGMT and lower TGase-2 may be predictors of good response to sunitinib. Independent of the treatment, in the entire group the ones with higher MGMT and lower TGase-2 have better survival. All these results are not statistically significant.